On-line Clean-up System of Plasma Sample for Simultaneous Determination of Morphine and Its Metabolites in Cancer Patients by High-Performance Liquid Chromatography

Konishi, Masaharu; Hashimoto, Hiroshi

doi:10.1002/jps.2600790503

Cited by 28 publications

(3 citation statements)

References 26 publications

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“…Electrochemical detection of morphine and M6G and ultraviolet detection of M3G were simultaneously accomplished using a column switching technique. 11 Detection limits were 2 ng/ mL for morphine, 40 ng/mL for M3G and 4 ng/mL for M6G. Interassay coefficients of variation were less than 4% at concentrations five times higher than the detection limits for all three compounds.…”

Section: Blood Sampling and Plasma Concentration Analysesmentioning

confidence: 80%

The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment

Takahashi¹,

Ohara²,

Yamanaka³

et al. 2003

Palliat Med

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To provide additional pharmacokinetic evidence for the oral-to-parenteral relative potency ratio of 1:2 to 1:3 for chronic morphine use in a palliative care setting, we determined the plasma concentrations of morphine and its major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in hospitalized advanced cancer patients maintained on long-term oral or intravenous morphine. There were significant linear correlations between daily doses of morphine and plasma concentrations (molar base) of morphine, M3G and M6G for both routes of administration. The oral-to-intravenous relative ratios of the regression coefficients were 2.9 for morphine and 1.8 for morphine» / M6G. The morphine kinetic variables were not significantly influenced by any hepato-renal biochemical markers. These results support the commonly used oral-to-intravenous relative potency ratio of 1:2 to 1:3 in patients with cancer pain receiving chronic morphine treatment.

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Section: Blood Sampling and Plasma Concentration Analysesmentioning

confidence: 80%

The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment

Takahashi¹,

Ohara²,

Yamanaka³

et al. 2003

Palliat Med

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“…The plasma was separated by centrifugation and frozen at Ϫ 20 Њ C. It was later analyzed for morphine, M-6-G, and M-3-G concentrations using high-performance liquid chromatography (HPLC). 36 The lowest measurable concentrations were 0.2 ng/mL, 0.5 ng/mL, and 10 ng/mL for morphine, M-6-G, and M-3-G, respectively. Between-day and within-day coefficients of variation were below 5.4%, and the mean recoveries ranged from 99% to 104%.…”

Section: Assaymentioning

confidence: 88%

Increased Plasma Morphine Metabolites in Terminally Ill Cancer Patients with Delirium

Morita

Tei

Tsunoda

et al. 2002

Journal of Pain and Symptom Management

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Delirium often causes severe distress for terminally ill cancer patients, and treatment of underlying pathologies is important to achieve symptom alleviation. Although accumulation of morphine metabolites may play an important role in development of delirium, empirical findings are conflicting due to a large inter-individual variation in morphine-related concentrations. To explore intra-individual changes of morphine metabolite concentrations before and after occurrence of terminal delirium, a prospective observational study was performed on terminally ill cancer patients. Among 131 consecutive hospice inpatients, 16 samples from 8 patients who received two blood samplings before and after development of delirium were analyzed. Delirium developed a median of 5 days before death, and clinical causes were attributed to multi-organ failure. Plasma concentrations of morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) significantly increased after development of delirium within the same patient. Mean normalized concentrations of M-6-G and M-3-G elevated from 1.24 +/- 1.06 to 2.94 +/- 3.52 ng/mL/mg (P = 0.016), and from 7.46 +/- 4.75 to 15.4 +/- 13.2 ng/mL/mg (P = 0.016), respectively. Normalized morphine concentration increased with a marginal statistical significance from 0.54 +/- 0.27 to 0.83 +/- 0.22 ng/mL/mg (P = 0.055). In conclusion, plasma concentrations of M-6-G and M-3-G were significantly higher after development of terminal delirium than before. It is suggested that accumulations of morphine metabolites can contribute to development of delirium in cancer patients whose death is impending.

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“…Gas chromatography (GC) and high-performance liquid chromatography (HPLC) are the most widely used separation techniques for analyses of drugs of abuse (Lurie et al, 1982(Lurie et al, , 1987(Lurie et al, , 1994Konishi and Hashimoto, 1990;Milne et al, 1991;Virag et al, 1996;Fryirs et al, 1997). In contrast to these techniques, capillary electrophoresis (CE) is a high-resolution technique with a relatively easy set-up procedures and greater economy of operation.…”

mentioning

confidence: 99%

On the perspectives of capillary electrophoresis modes for the determination of morphine in human plasma without sample pretreatment

Emara

Darwish

Youssef

et al. 2003

Biomedical Chromatography

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Screening and confirmation of drugs of abuse in body fluids are important for the medicinal treatment and form the legal basis of court judgments. A fast and precise identification of toxic substances is necessary. Morphine was determined in human plasma by capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) using sample stacking mode. The electrophoretic separation was performed in an uncoated fused-silica capillary, 70 cm long to the detector, with an additional 10 cm to the cathode (75 microm i.d. and 360 microm o.d.). The UV absorbance detection was set at 190 nm. The electrophoretic buffers were prepared from 60 to 300 mm disodium tetraborate decahydrate, pH 10.5. Sodium dodecyl sulfate was added to the final solution in a concentration of 60 mm for MECC. All electrophoretic separations were carried out at 10 kV and the capillary temperature was ambient (25 degrees C). A linear calibration graph was obtained in the concentration range studied (50-5000 ng/mL). Several samples of drug-free plasma were checked for potential endogenous interference and the results showed no interference from the endogenous components, which co-migrated with morphine. As little as 50 ng/mL of morphine could be successfully analyzed by MECC in the concentration mode with acceptable precision. It is possible to determine morphine directly in plasma at therapeutic concentrations.

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On-line Clean-up System of Plasma Sample for Simultaneous Determination of Morphine and Its Metabolites in Cancer Patients by High-Performance Liquid Chromatography

Cited by 28 publications

References 26 publications

The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment

The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment

Increased Plasma Morphine Metabolites in Terminally Ill Cancer Patients with Delirium

On the perspectives of capillary electrophoresis modes for the determination of morphine in human plasma without sample pretreatment

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